Cell Membrane Transport

• The cell membrane acts as a barrier, controlling the entry and exit of substances.
• Selective permeability allows only specific molecules to pass through the cell membrane.
• The membrane maintains ion gradients by regulating ion concentrations within the cell.

Molecule Movement

• Oxygen (O₂) easily passes through the cell membrane.
• Oxygen (O₂) is a type of molecule that diffuses freely.
• Large, uncharged molecules like glucose are transported via facilitated diffusion.

Passive vs. Active Transport

• Passive transport involves movement down a concentration gradient and does not require ATP.
• Active transport uses ATP to move molecules against their concentration gradient.
• In coupled transport, one molecule moves against its gradient using energy from another molecule such as the sodium-glucose symport.
• Sodium-glucose transporter is an example of a symport.

Ion Concentration & Gradients

• Sodium (Na⁺) has a higher extracellular concentration.
• In neurons at rest, potassium is inside, and sodium is outside.

Membrane Proteins

• Channel proteins facilitate diffusion, allowing molecules to pass through.
• Carrier proteins change shape to move molecules like glucose.
• Ion channels facilitate the passive movement of ions down their concentration gradient.

Pumps

• Sodium-potassium ATPase pumps sodium out and potassium in, against their gradients.
• The main function of the Na⁺/K⁺ ATPase pump is to help maintain electrical charge.
• ATP hydrolysis drives the Na⁺/K⁺ pump.

Calcium Transport

• The sarcoplasmic reticulum stores Ca²⁺ for muscle contraction.
• Calcium pumps move Ca²⁺ out of or into the sarcoplasmic reticulum (SR).

Neurophysiology: Membrane Potential & Action Potentials

• The resting membrane potential is -70 mV.
• Depolarization is caused by Na⁺ rushing into the cell.
• During repolarization, Na⁺ channels close, and K⁺ channels open.
• The Nernst equation calculates the voltage where there is no net ion movement.

Ion Channels in Neurons

• Voltage-gated ion channels transmit electrical signals.
• At the axon terminal, Ca²⁺ channels open.
• Ca²⁺ movement triggers vesicle fusion with the membrane for neurotransmitter release.
• Stress-gated ion channels in the ear open in response to sound vibrations.

Protein Synthesis & Targeting: Where & How

• The cytosol is responsible for most protein synthesis.
• Mitochondria's primary role is ATP production.
• Protein synthesis from nuclear DNA begins in the cytoplasm.

Endoplasmic Reticulum (ER)

• Secretory and membrane proteins are made in the rough ER.
• SRP slows translation and guides proteins to the ER.
• Chaperones help refold proteins in the ER.
• During ER entry, the signal peptide is cleaved off.
• Peptidase in the ER cleaves the signal peptide.

Transport into Organelles

• Proteins enter mitochondria via receptor binding and membrane translocation.
• Most mitochondrial proteins come from nuclear DNA and are made in the cytoplasm.
• Mitochondria have their own DNA and protein synthesis machinery.

Vesicle Transport & Secretion: Vesicle Formation & Targeting

• Rab protein guides the vesicle to the membrane.
• v-SNARE and t-SNARE are involved in the fusion of vesicles to the target membrane.
• Clathrin is a protein coat for vesicle transport to the plasma membrane.
• Tethering proteins are the key docking structure.

Secretion Types

• Constitutive secretion is continuous and does not require a stimulus.

Endocytosis & Endosomes

• Receptor-mediated endocytosis involves the uptake of specific molecules via receptors.
• Endosomes sort endocytosed material.

Golgi Apparatus & Lysosomes

• The Golgi apparatus sorts, modifies, and packages proteins.
• Lysosomes are the organelle responsible for intracellular degradation.
• The environment for lysosomal enzymes is acidic (pH < 7).
• Undigested materials accumulate with a mutation in a lysosomal enzyme gene.

Smooth ER & Detox

• The smooth ER is involved in lipid synthesis and detoxifying hydrophobic toxins.
• Cytochrome P450 mutation results in impaired detox in the smooth ER.

Nucleus & Protein Import

• Nuclear pores regulate movement in and out of the nucleus.
• Nuclear transport receptors bind proteins with NLS (nuclear localization signals) and bring them into the nucleus.
• When Ran-GTP is hydrolyzed, the receptor is released to bind another cargo.

Chapter 12: Membrane Transport – Study Guide

• Understand membrane roles, molecular transport mechanisms, distinctions between passive/active transport, channel vs. transporter comparison, gradient understanding, & channel regulation.

Functions of Cell Membranes

• Compartmentalization separates cellular processes.
• Scaffolding provides structure for proteins.
• Ion imbalance creates gradients.
• Energy transformation occurs here.
• Exchange of gases, water, nutrients, and waste.
• Catalysis of reactions.
• Signal transduction is facilitated.
• Transport and binding takes place.

Membrane Permeability

• Lipid bilayers are selectively permeable.
• Transport proteins move impermeable molecules.
• Water's hydration shell affects permeability.

Membrane Transport Proteins: Two Main Types

• Channels have hydrophilic pores, facilitate passive transport and are selective based on size/charge.
• Transporters (carriers) bind and move specific solutes, performing active or passive transport.

Types of Transport

• Simple diffusion is entropy-driven and moves from high to low concentration.
• Passive transport is facilitated by channels/transporters and driven by a concentration gradient.
• Active transport requires energy (ATP or another gradient) and moves solutes from low to high concentration.
  • Calcium Pumps maintain low intracellular Ca²⁺.
  • Na⁺/K⁺ ATPase pumps 3 Na⁺ out and 2 K⁺ in.

Coupled Transport

• Coupled transport uses one solute's gradient to move another.
  • Symport moves both solutes in same direction (e.g., Na⁺/glucose).
  • Antiport moves solutes in opposite directions.

Gradient Power

• Na⁺ gradient (from Na⁺/K⁺ ATPase) is used widely in animal cells.
• H⁺ gradient is used in plants, fungi, and bacteria.

Ion Channels

• Ion channels are highly ion-selective and utilizes the following gating mechanisms:
  • Voltage-gated channels respond to changes in membrane potential (e.g., Na⁺, K⁺).
  • Ligand-gated channels respond to neurotransmitters.
  • Mechanically-gated channels respond to physical stimuli (e.g., cochlea hair cells).

Electrochemical Gradient

  - A combination of concentration gradient and membrane voltage.
  - Maintained by Na⁺/K⁺ ATPase and K⁺ leak channels.
  - Crucial for resting membrane potential (≈ -70 mV).

Action Potentials

1. Depolarization: Voltage change opens Na⁺ channels, and Na⁺ rushes in.
2. Repolarization: Na⁺ channels inactivate, and K⁺ channels open, and K⁺ exits.
3. Reset: Na⁺/K⁺ pump reestablishes gradient.

Signal Transmission (Neurons)

  - An electrical signal opens Ca²⁺ channels, and Ca²⁺ enters.
  - Vesicle fusion occurs, and neurotransmitters are released.
  - Neurotransmitters bind ligand-gated channels on the next neuron.

Clinical Relevance

  - Ion channel mutations can cause serious health issues.

Tips

 - Focus on concepts and mechanisms, not memorizing every figure
 - Understand the flow of ions and how gradients are created/used
 - Make sure to grasp differences between:
     - Passive vs. Active Transport
     - Channels vs. Transporters
     - Voltage-gated vs. Ligand-gated channels

Chapter 15 Study Guide: Intracellular Compartments and

Transport

Objectives

  -Understand how proteins are targeted to different cell compartments.
  -Understand organelle functions in the endomembrane system.
  -Know how substances move into and out of cells.

Membrane-Enclosed Organelles

  -All eukaryotic cells contain membrane-bound organelles.
  -Proteins begin synthesis in the cytoplasm.
  -Proteins are directed to their locations by signal sequences.

Protein Targeting & Signal Sequences

  -Signal sequences are necessary and sufficient for targeting.
  -Three mechanisms for import into organelles:
       1. Transport through nuclear pores
       2. Transport across membranes (e.g., mitochondria, chloroplasts)
       3.Transport by vesicles (e.g., ER, Golgi, lysosomes)

Nuclear Transport

  -Small molecules (sugars, salts) pass freely.
  -Large molecules (proteins, mRNA) require nuclear localization signals (NLS) and
   transport receptors.
  -Requires GTP and a GTP-binding protein called Ran.

Mitochondria & Chloroplasts

  -Mitochondria evolved from respiratory bacteria.
  -Most proteins are encoded in nuclear DNA and imported.
  -Proteins must be unfolded, passed through translocators, and refolded with help from chaperones.
  -Chloroplasts use a similar system but have more DNA.

Endomembrane System

 -Includes: ER, Golgi, plasma membrane, lysosomes, vacuoles, secretory vesicles

Endoplasmic Reticulum (ER)

  -Smooth ER:
       -Lipid synthesis
       -Calcium storage
       -Detoxification via Cytochrome P450
  -Rough ER:
       -Site of protein synthesis
       -Uses Signal Recognition Particle (SRP) to direct ribosomes
       -Translation resumes as protein enters ER via a translocator

Protein Folding & Processing

  -Proteins enter the ER co-translationally.
  -Signal peptide is cleaved inside ER lumen.
  -Transmembrane proteins use start/stop transfer sequences to insert into the membrane.

Vesicle Transport

 -Proteins move from ER to Golgi to final destination in vesicles.
 -Vesicle movement is motor protein-driven along the cytoskeleton.

Golgi Apparatus

 -Further modifies and sorts proteins/lipids.
 -Uses receptors and structural tags to package proteins.

Vesicle Coating & Targeting

 -Vesicles form via coat proteins:
       -COP: ER ↔ Golgi
       -Clathrin: Golgi ↔ Plasma membrane
 -Targeting proteins:
       -Rab (docking)
       -SNAREs (fusion)

Exocytosis

 -Constitutive secretion: continuous (e.g., mucus)
 -Regulated secretion: triggered (e.g., insulin, neurotransmitters)

Endocytosis

 -Phagocytosis: cell eating (large particles)
 -Pinocytosis: cell drinking (fluids/small molecules)
 -Receptor-mediated endocytosis: specific uptake using receptors

Endosomes & Lysosomes

-Endosomes: sort endocytosed material -Recycling to membrane -Transport to lysosome -Lysosomes: acidic, enzyme-filled organelles that digest materials -Defects in lysosomes → storage diseases

Research & Disease Insight

  -GFP-fusion proteins help visualize trafficking
  -Mutants with transport defects help identify pathways

BIO 2600 – Exam 3 Study Guide

Membrane Structure & Function (Chapter 12)

1. Membrane Basics

   • Barrier, communication, transport and compartmentalization are the functions of a membrane
   • Membrane potential - the charge difference depending on K+ being higher inside and Na+ being higher outside
   • Semi-permeable membrane
     • Can easily passively transfer small, nonpolar molecules
     • Water can diffuse readily due to small size
     • Large and polar molecules along with ions, cannot pass easily.

2. Transport Types -Simple Diffusion - With gradient, not requiring ATP, and does not involve proteins -Passive Transport - With gradient, not requiring ATP, and involves channels/carriers -Active Transport - Against gradient, uses ATP, and uses specific carriers

3. Transport Proteins -Channels - Open, passive, based on size/charge -Carriers - Bind to solutes, undergo a shape change

4. Coupled Transport -Symport - two molecules going in the same direction -Antiport - molecules moving in opposite directions -Na drives the coupled transport of amino acids and glucose in animal cells

5. Pumps and Ion Gradients: -Na+/K+ pump (ATPase): Active, pumps 3 Na+ out, while pumping 2 K+ in. -Ca2+ pumps: Responsible for maintaining a low, intracellular [Ca2+] through sequestration within the ER/SR.

6. Ion Channels and Signals: -Channels are mechanically gated, voltage-gated, or ligand gated. -Mechanically gated channels in ear stereocilia open via vibration.

7. Action Potentials: Signals that trigger rapid, long-distance responses -Rapid voltage changes due to Na influx and K efflux -Propagation: Spreads down the membrane -Depolarization: Inside the membrane becomes more positive in response to influx of Na ions

8. Synaptic Transmissions:

Calcium influx triggers neurotransmitter release into synapse

Intracellular Compartments & Protein Transport (Chapter 15)

Protein Synthesis

- Occurs in cytoplasm
- Proteins are sent to organelles via signal sequences

Targeting Mechanisms

   -Gated Transport - Requires nuclear pores, moving from cytosol into nucleus
   -Translocators: Using a pore, proteins move from from water (unfolded), from the cytosol, to either the mitochondria (power production) or chloroplasts (food creation in plants)
   -Vesicular:  Moving proteins, via transport vesicles, from the ER, to the PM, golgi or lysosomes

Signal Sequences

 Direct proteins to correct destination
 Depend on final location

Nuclear Import

Requires Ran-GTP and special nuclear transport receptors
Small molecules can enter freely, where large molecules must be highly regulated

Mitochondria and Chloroplasts

-Mitochondria is thought to have evolved from bacteria
-Most proteins coded by DNA are moved from their creation point in the cytosol, into the organelle. 
-This requires them to be unfolded on the way in (via translocators), and then refolded with chaperones on the way out. 

ER Functions

-Smooth ER: Lipid synthesis/Ca2+ storage/Detoxification -Rough ER: Protein synthesis via the secretary pathway

ER Protein Translocation

1. Ribosomes begin synthesis
2. Signal peptide -> SRP -> SRP Receptor
3. Protein enters via the translocator
4. Proteins are folded by chaperones
5. Special stop signal molecules halt the protein entry, and a signal peptide is cleaved

Vesicular Transport & Secretion (Chapter 15, cont.)

Vesicle Movement

-Vesicles move with motor proteins on a cytoskeleton
-They transport lipids and proteins between the ER, Golgi and PM

Coats & Targeting:

-Clathrin: Aids the Golgi complex to move towards the Plasma Membrane
-COP:  Aids the ER to go towards the Golgi complex
-Vesicle targeting: Uses Rab (vesicle) + tethering proteins and SNARE’s for movements

Secretion Types:

-Regulated: Need special Stimulus i.e. hormones for release
-Constitutive: Continuous

Endocytosis & Lysosomes

Endocytosis Types:

-Phagocytosis: Capturing large extracellular particles -Pinocytosis: Capturing extracellular fluids/particles

Lysosomes:

Intracellular digestions using acidic enzymes Failure can lead to a build-up of undigested material, aka ‘glycosphingolipid disease’

Cell Signaling (Chapter 16)

Signal reception:

Cell must have receptors to capture signals for any sort of response

Signal Receptors and Transduction

Binds receptor to trigger an intracellular signal Pathway functions to relay, amplify, integrate and distribute responses in the cell